Value of CT-Based Deep Learning Model in Differentiating Benign and Malignant Solid Pulmonary Nodules ≤ 8 mm.

RATIONALE AND OBJECTIVES: We examined the effectiveness of computed tomography (CT)-based deep learning (DL) models in differentiating benign and malignant solid pulmonary nodules (SPNs) ≤ 8 mm. MATERIALS AND METHODS: The study patients (n = 719) were divided into internal training, internal validation, and external validation cohorts; all had small SPNs and had undergone preoperative chest CTs and surgical resection. We developed five DL models incorporating features of the nodule and five different peri-nodular regions with the Multiscale Dual Attention Network (MDANet) to differentiate benign and malignant SPNs. We selected the best-performing model, which was then compared to four conventional algorithms (VGG19, ResNet50, ResNeXt50, and DenseNet121). Furthermore, another five DL models were constructed using MDANet to distinguish benign tumors from inflammatory nodules and the one performed best was selected out. RESULTS: Model 4, which incorporated the nodule and 15 mm peri-nodular region, best differentiated benign and malignant SPNs. The model had an area under the curve (AUC), accuracy, recall, precision, and F1-score of 0.730, 0.724, 0.711, 0.705, and 0.707 in the external validation cohort. Model 4 also performed better than the other four conventional algorithms. Model 8, which incorporated the nodule and 10 mm peri-nodular region, was the best model for distinguishing benign tumors from inflammatory nodules. The model had an AUC, accuracy, recall, precision, and F1-score of 0.871, 0.938, 0.863, 0.904, and 0.882 in the external validation cohort. CONCLUSION: The study concludes that CT-based DL models built with MDANet can accurately discriminate among small benign and malignant SPNs, benign tumors and inflammatory nodules.

The differential computed tomography features between small benign and malignant solid solitary pulmonary nodules with different sizes.

Background: Computed tomography (CT) has been widely known to be the first choice for the diagnosis of solid solitary pulmonary nodules (SSPNs). However, the smaller the SSPN is, the less the differential CT signs between benign and malignant SSPNs there are, which brings great challenges to their diagnosis. Therefore, this study aimed to investigate the differential CT features between small (≤15 mm) benign and malignant SSPNs with different sizes. Methods: From May 2018 to November 2021, CT data of 794 patients with small SSPNs (≤15 mm) were retrospectively analyzed. SSPNs were divided into benign and malignant groups, and each group was further classified into three cohorts: cohort I (diameter ≤6 mm), cohort II (6 mm < diameter ≤8 mm), and cohort III (8 mm < diameter ≤15 mm). The differential CT features of benign and malignant SSPNs in three cohorts were identified. Multivariable logistic regression analyses were conducted to identify independent factors of benign SSPNs. Results: In cohort I, polygonal shape and upper-lobe distribution differed significantly between groups (all P<0.05) and multiparametric analysis showed polygonal shape [adjusted odds ratio (OR): 12.165; 95% confidence interval (CI): 1.512-97.872; P=0.019] was the most effective variation for predicting benign SSPNs, with an area under the receiver operating characteristic curve (AUC) of 0.747 (95% CI: 0.640-0.855; P=0.001). In cohort II, polygonal shape, lobulation, pleural retraction, and air bronchogram differed significantly between groups (all P<0.05), and polygonal shape (OR: 8.870; 95% CI: 1.096-71.772; P=0.041) and the absence of pleural retraction (OR: 0.306; 95% CI: 0.106-0.883; P=0.028) were independent predictors of benign SSPNs, with an AUC of 0.778 (95% CI: 0.694-0.863; P<0.001). In cohort III, 12 CT features showed significant differences between groups (all P<0.05) and polygonal shape (OR: 3.953; 95% CI: 1.508-10.361; P=0.005); calcification (OR: 3.710; 95% CI: 1.305-10.551; P=0.014); halo sign (OR: 6.237; 95% CI: 2.838-13.710; P<0.001); satellite lesions (OR: 6.554; 95% CI: 3.225-13.318; P<0.001); and the absence of lobulation (OR: 0.066; 95% CI: 0.026-0.167; P<0.001), air space (OR: 0.405; 95% CI: 0.215-0.764; P=0.005), pleural retraction (OR: 0.297; 95% CI: 0.179-0.493; P<0.001), bronchial truncation (OR: 0.165; 95% CI: 0.090-0.303; P<0.001), and air bronchogram (OR: 0.363; 95% CI: 0.208-0.633; P<0.001) were independent predictors of benign SSPNs, with an AUC of 0.869 (95% CI: 0.840-0.897; P<0.001). Conclusions: CT features vary between SSPNs with different sizes. Clarifying the differential CT features based on different diameter ranges may help to minimize ambiguities and discriminate the benign SSPNs from malignant ones.

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

CTRP13 Mitigates Endothelial Cell Ferroptosis via the AMPK/KLF4 Pathway: Implications for Atherosclerosis Protection.

BACKGROUND C1q/tumor necrosis factor-related protein 13 (CTRP13) preserves endothelial function and possesses anti-oxidation activity. However, its effects on ferroptosis of human umbilical vein endothelial cells (HUVECs) remain unclear. We investigated the effects of CTRP13 on HUVEC ferroptosis induced by oxidized low-density lipoprotein (ox-LDL) and explored the underlying mechanisms of CTRP13 against ferroptosis via the AMPK/KLF4 pathway. MATERIAL AND METHODS Cell Counting Kit-8 assay was used to evaluate cell viability. Lactate dehydrogenase activity and malondialdehyde content analysis were performed to evaluate the cell membrane integrity and lipid peroxidation. Mito-Tracker, JC-1, and 2',7'-dichlorofluorescein di-acetate were used to evaluate the biological activity of mitochondria, mitochondrial membrane potential, and reactive oxygen species (ROS) in endothelial cells. The ferroptosis indicator expressions, recombinant solute carrier family 7, member 11, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 were examined using real-time reverse transcription-polymerase chain reaction and Western blot. Immunofluorescence staining detected GPX4 location in endothelial cells. RESULTS The results demonstrate that CTRP13 (450 ng/mL) prevented HUVEC ferroptosis by inhibiting ROS overproduction and mitochondrial dysfunction, and CTRP13 accelerated antioxidant enzyme expression levels, such as heme oxygenase 1, superoxide dismutase 1, and superoxide dismutase 2, compared with the ox-LDL (100 µg/mL) group for 48 h. Additionally, CTRP13 treatment increased p-AMPK/AMPK expression by 47.65% (P<0.05) while decreasing Krüppel-like factor 4 expression by 37.43% (P<0.05) in ox-LDL-induced HUVECs and elucidated the protective effect on endothelial dysfunction from ferroptosis. CONCLUSIONS These findings provide new insights for understanding the effects and mechanism of CTRP13 on preventing endothelial cell ferroptosis.

Solitary lung adenocarcinoma: follow-up CT, pathological-molecular characteristics, and surgical prognosis for different morphological classifications.

OBJECTIVE: To investigate the dynamic changes during follow-up computed tomography (CT), histological subtypes, gene mutation status, and surgical prognosis for different morphological presentations of solitary lung adenocarcinomas (SLADC). MATERIALS AND METHODS: This retrospective study compared dynamic tumor changes and volume doubling time (VDT) in 228 patients with SLADC (morphological types I-IV) who had intermittent growth during follow-ups. The correlation between the morphological classification and histological subtypes, gene mutation status, and surgical prognosis was evaluated. RESULTS: Among the 228 patients, 66 (28.9%) were classified as type I, 123 (53.9%) as type II, 16 (7%) as type III, and 23 (10.1%) as type IV. Type I had the shortest VDT (254 days), followed by types IV (381 days) and III (501 days), and then type II (993 days) (p < 0.05 each). Type I had a greater proportion of solid/micropapillary-predominant pattern than type II, and the lepidic-predominant pattern was more common in type II and III than in type I (p < 0.05 each). Furthermore, type II and IV SLADCs were correlated with positive epidermal growth factor receptor mutation (p < 0.05 each). Lastly, the Kaplan-Meier curves showed that the disease-free survival was longest for patients with type II tumors, followed by those with type III and IV tumors, and then those with type I tumors (p < 0.001 each). CONCLUSION: A good understanding of the natural progression and pathological-molecular characteristics of different morphological SLADC types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. CRITICAL RELEVANCE STATEMENT: A good understanding of the natural progression and pathological-molecular characteristics of different morphological solitary lung adenocarcinoma types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes. KEY POINTS: • Type I-IV solitary lung adenocarcinomas exhibit varying natural progression on serial CT scans. • Morphological classification of solitary lung adenocarcinomas predicts histological subtype, gene status, and surgical prognosis. • This classification of solitary lung adenocarcinomas may help improve diagnostic, therapeutic, and prognosticating abilities.

Development and validation of a CT algorithm for the identification of nonperforated duodenal bulb ulcer.

PURPOSE: To assess the value of multiplanar computed tomography (CT) in the diagnosis of nonperforated duodenal bulb ulcer (NPDBU). METHOD: We retrospectively analyzed data from 135 patients with NPDBU (ulcer group) and 150 patients with a normal duodenal bulb (control group) who underwent contrast-enhanced abdominal CT and were diagnosed via upper endoscopy from January 2018 to February 2022. The clinical and CT features were compared between the two groups. Independent prognostic factors for diagnosing NPDBU were determined using binary logistic regression analysis. An external validation cohort to determine the model's efficiency comprised 80 patients from another center. RESULTS: Gastrointestinal bleeding was more frequent in patients with NPDBU than in those without (p < 0.001). No significant differences in age and sex were observed between the groups (all p > 0.05). The duodenal bulbar wall was significantly thicker in the ulcer group than in the control group, as determined using CT (p < 0.001). Irregular mucosal surface, layered enhancement, and blurred fat space around the duodenal bulb were more common in the ulcer group than in the control group (all p < 0.001). Binary logistic regression analysis revealed that gastrointestinal bleeding, wall thickness of ≥ 4.85 mm, irregular mucosal surface, and blurred peripheral fat space were the most significant variations associated with NPDBU, with an area under the curve (AUC) of 0.974. The external validation cohort had an AUC of 0.916. CONCLUSIONS: Careful multiplanar CT interpretation suggests the underlying presence of NPDBU and allows timely endoscopic verification and appropriate treatment.

A landscape of Long non-coding RNAs reveals the leading transcriptome alterations in murine aorta during aging.

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.

Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.

Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.

Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis.

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension. METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia. RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group. CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo .

Combined model of radiomics, clinical, and imaging features for differentiating focal pneumonia-like lung cancer from pulmonary inflammatory lesions: an exploratory study.

BACKGROUND: Only few studies have focused on differentiating focal pneumonia-like lung cancer (F-PLC) from focal pulmonary inflammatory lesion (F-PIL). This exploratory study aimed to evaluate the clinical value of a combined model incorporating computed tomography (CT)-based radiomics signatures, clinical factors, and CT morphological features for distinguishing F-PLC and F-PIL. METHODS: In total, 396 patients pathologically diagnosed with F-PLC and F-PIL from two medical institutions between January 2015 and May 2021 were retrospectively analyzed. Patients from center 1 were included in the training (n = 242) and internal validation (n = 104) cohorts. Moreover, patients from center 2 were classified under the external validation cohort (n = 50). The clinical and CT morphological characteristics of both groups were compared first. And then, a clinical model incorporating clinical and CT morphological features, a radiomics model reflecting the radiomics signature of lung lesions, and a combined model were developed and validated, respectively. RESULTS: Age, gender, smoking history, respiratory symptoms, air bronchogram, necrosis, and pleural attachment differed significantly between the F-PLC and F-PIL groups (all P < 0.05). For the clinical model, age, necrosis, and pleural attachment were the most effective factors to differentiate F-PIL from F-PLC, with the area under the curves (AUCs) of 0.838, 0.819, and 0.717 in the training and internal and external validation cohorts, respectively. For the radiomics model, five radiomics features were found to be significantly related to the identification of F-PLC and F-PIL (all P < 0.001), with the AUCs of 0.804, 0.877, and 0.734 in the training and internal and external validation cohorts, respectively. For the combined model, five radiomics features, age, necrosis, and pleural attachment were independent predictors for distinguishing between F-PLC and F-PIL, with the AUCs of 0.915, 0.899, and 0.805 in the training and internal and external validation cohorts, respectively. The combined model exhibited a better performance than had the clinical and radiomics models. CONCLUSIONS: The combined model, which incorporates CT-based radiomics signatures, clinical factors, and CT morphological characteristics, is effective in differentiating F-PLC from F-PIL.

Differential diagnosis of localized pneumonic-type lung adenocarcinoma and pulmonary inflammatory lesion.

BACKGROUND: In clinical practice, a number of delayed diagnoses of localized pneumonic-type lung adenocarcinoma (L-PLADC) mimicking pneumonia have been identified due to the lack of knowledge regarding the radiological findings associated with this condition. Here, we defined L-PLADC as a special type of lung adenocarcinoma that presents as a focal consolidation involving < 50% of the area of a lobe and aimed to investigate the differential clinical and imaging features between L-PLADC and localized pulmonary inflammatory lesion (L-PIL). RESULTS: The data of 120 patients with L-PLADC and 125 patients with L-PIL who underwent contrast-enhanced chest computed tomography (CT) scan were retrospectively analyzed. For clinical characteristics, older age, women, nonsmokers, and no symptom were more common in L-PLADC (all p < 0.001). With regard to CT features, air bronchogram, irregular air bronchogram, ground-glass opacity (GGO) component, and pleural retraction were more frequently observed in L-PLADC, while necrosis, satellite lesions, halo sign, bronchial wall thickening, interlobular septa thickening, pleural attachment, and pleural thickening were more commonly seen in L-PIL (all p < 0.001). Multivariate analysis showed age ≥ 58 years, female sex, GGO component, irregular air bronchogram, pleural retraction, and the absence of necrosis and pleural attachment were the most effective variations associated with L-PLADC with an AUC of 0.979. Furthermore, an external validation cohort containing 62 patients obtained an AUC of 0.929. CONCLUSIONS: L-PLADC and L-PIL have different clinical and imaging characteristics. An adequate understanding of these differential features can contribute to the early diagnosis of L-PLADC and the subsequent therapeutic strategy.

Relationship between non-culprit lesion plaque characteristics changes and in-stent neoatherosclerosis formation: 1-year follow-up optical coherence tomography study.

The relationship between the in-stent neoatherosclerosis (ISNA) formation and the plaque's characteristic changes in the non-culprit lesion is unclear. We aim to investigate the plaque characteristics changes at non-culprit lesions between patients with ISNA and without ISNA formation at 1-year follow-up. We retrospectively enrolled patients who had DES implantation in de novo lesion and underwent immediately after stenting and 1-year follow-up optical coherence tomography (OCT) examination. OCT-defined ISNA was defined as the presence of lipid-laden neointima or calcification within the culprit stent with a longitudinal extension of ≥1 mm. Non-culprit lesions were divided into two groups: ISNA group (with ISNA) and non-ISNA group (without ISNA). Plaque characteristics of non-culprit lesions were evaluated at baseline and 1-year follow-up. In total, 89 patients with 89 non-culprit lesions (ISNA: n = 37; non-ISNA: n = 52) were included in the analyses. The lesions in the ISNA group show a smaller minimum lumen area compared to the non-ISNA group at 1-year follow-up (2.57 ± 1.08 mm2 versus 3.20 ± 1.62 mm2, p = 0.044). The lesions of the ISNA group show a significant decrease in minimum lumen area changes percent (-7.25% versus 6.46%, p = 0.039). And there are more lesions with minimum lumen area (64.9% versus 38.5%, p = 0.014) and minimum lumen diameter (64.9% versus 40.4%, p = 0.023) decrease in the ISNA group. Furthermore, the lesions in ISNA group have more plaques with lipid core length increase (25.0% versus 10.0%, p = 0.040), more plaques with FCT decrease (50.0% versus 74.0%, p = 0.027) and less TCFA change to non-TCFA (33.3% versus 87.5%, p = 0.010). The plaque characteristic changes in non-culprit lesions are closely related to ISNA formation. The ISNA formation may accompany by a tardier plaque stabilization process in non-culprit lesions.

C1q/TNF-Related Protein 9 Attenuates Atherosclerosis by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the AMPKα/KLF4 Signaling Pathway.

Hyperglycemia-induced endothelial cell senescence has been widely reported to be involved in the pathogenesis of type 2 diabetes mellitus‒accelerated atherosclerosis. Thus, understanding the underlying mechanisms and identifying potential therapeutic targets for endothelial cell senescence are valuable for attenuating atherosclerosis progression. C1q/tumor necrosis factor-related protein 9 (CTRP9), an emerging potential cardiokine, exerts a significant protective effect with respect to atherosclerosis, particularly in endothelial cells. However, the exact mechanism by which CTRP9 prevents endothelial cells from hyperglycemia-induced senescence remains unclear. This study aimed to investigate the effects of CTRP9 on hyperglycemia-induced endothelial cell senescence and atherosclerotic plaque formation in diabetic apolipoprotein E knockout (ApoE KO) mice. Human umbilical vein endothelial cells (HUVECs) were cultured in normal glucose (5.5 mM) and high glucose (40 mM) with or without recombinant human CTRP9 protein (3 µg/ml) for 48 h. Purified lentiviruses overexpressing CTRP9 (Lv-CTRP9) and control vectors containing green fluorescent protein (Lv-GFP) were injected via the tail vein into streptozotocin-induced diabetic ApoE KO mice. Results revealed that exposure of HUVECs to HG significantly increased the expression of Krüppel-like factor 4 (KLF4) and cyclin-dependent kinase inhibitor p21 (p21) and decreased that of telomerase reverse transcriptase (TERT). Treatment with recombinant human CTRP9 protein protected HUVECs from HG-induced premature senescence and dysfunction. CTRP9 promoted the phosphorylation of AMP-activated kinase (AMPK), attenuated the expression of KLF4 and p21 induced by HG, and increased the expression of TERT in HUVECs. Furthermore, in the background of AMPKα knockdown or KLF4 activation, the protective effects of CTRP9 were abolished. In-vivo experiments showed that the overexpression of CTRP9 inhibited vascular senescence and reduced atherosclerotic plaque formation in ApoE KO mice with diabetes. In conclusion, we demonstrate that KLF4 upregulation plays a crucial role in HG-induced endothelial senescence. This anti-atherosclerotic effect of CTRP9 may be partly attributed to the inhibition of HG-induced endothelial senescence through an AMPKα/KLF4-dependent mechanism, suggesting that CTRP9 could benefit further therapeutic approaches for type 2 diabetes mellitus‒accelerated atherosclerosis.

Pneumonic-type lung adenocarcinoma with different ranges exhibiting different clinical, imaging, and pathological characteristics.

BACKGROUND: Pneumonic-type lung adenocarcinoma (PLADC) with different ranges might exhibit different imaging and clinicopathological features. This study divided PLADC into localized PLADC (L-PLADC) and diffuse PLADC (D-PLADC) based on imaging and aimed to clarify the differences in clinical, imaging, and pathologic characteristics between the two new subtypes. RESULTS: The data of 131 patients with L-PLADC and 117 patients with D-PLADC who were pathologically confirmed and underwent chest computed tomography (CT) at our institute from December 2014 to December 2020 were retrospectively collected. Patients with L-PLADC were predominantly female, non-smokers, and without respiratory symptoms and elevated white blood cell count and C-reactive protein level, whereas those with D-PLADC were predominantly male, smokers, and had respiratory symptoms and elevated white blood cell count and C-reactive protein level (all p < 0.05). Pleural retraction was more common in L-PLADC, whereas interlobular fissure bulging, hypodense sign, air space, CT angiogram sign, coexisting nodules, pleural effusion, and lymphadenopathy were more frequent in D-PLADC (all p < 0.001). Among the 129 patients with surgically resected PLADC, the most common histological subtype of L-PLADC was acinar-predominant growth pattern (76.7%, 79/103), whereas that of D-PLADC was invasive mucinous adenocarcinoma (80.8%, 21/26). Among the 136 patients with EGFR mutation status, L-PLADC had a significantly higher EGFR mutation rate than D-PLADC (p < 0.001). CONCLUSIONS: L-PLADC and D-PLADC have different clinical, imaging, and pathological characteristics. This new imaging-based classification may help improve our understanding of PLADC and develop personalized treatment plans, with concomitant implications for patient outcomes.

Sex Differences in the Non-infarct-Related Artery-Based Quantitative Flow Ratio in Patients With ST-Elevation Myocardial Infarction: A Retrospective Study.

Introduction: It has been reported that sex has well-established relationships with the prevalence of coronary artery disease (CAD) and the major adverse cardiovascular events. Compared with men, the difference of coronary artery and myocardial characteristics in women has effects on anatomical and functional evaluations. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in acute myocardial infarction patients is unknown. This study aimed to evaluate the sex differences in the non-infarct-related artery (NIRA)-based QFR in patients with ST-elevation myocardial infarction (STEMI). Methods: In this study, 353 patients with STEMI who underwent angiographic cQFR assessment and interventional therapy were included. According to contrast-flow QFR (cQFR) standard operating procedures: reliable software was used to modeling the hyperemic flow velocity derived from coronary angiography in the absence of pharmacologically induced hyperemia. 353 patients were divided into two groups according to sex. A cQFR ≤0.80 was considered hemodynamically significant, whereas invasive coronary angiography (ICA) luminal stenosis ≥50% was considered obstructive. Demographics, clinical data, NIRA-related anatomy, and functional cQFR values were recorded. Clinical outcomes included the NIRA reclassification rate between men and women, according to the ICA and cQFR assessments. Results: Women were older and had a higher body mass index (BMI) than men. The levels of diastolic blood pressure, troponin I, peak creatine kinase-MB, low-density lipoprotein cholesterol, N terminal pro B-type natriuretic peptide, stent diameter, and current smoking rate were found to be significantly lower in the female group than in the male group. Women had a lower likelihood of a positive cQFR ≤0.80 for the same degree of stenosis and a lower rate of NIRA revascularization. Independent predictors of positive cQFR included male sex and diameter stenosis (DS) >70%. Conclusions: cQFR values differ between the sexes, as women have a higher cQFR value for the same degree of stenosis. The findings suggest that QFR variations by sex require specific interpretation, as these differences may affect therapeutic decision-making and clinical outcomes.

Remodelling of gut microbiota by Berberine attenuates trimethylamine N-oxide-induced platelet hyperreaction and thrombus formation.

Berberine is an extract derived from Chinese herbs with pleiotropic cardiovascular protective effects. However, the underlying mechanism remains unclear because of its poor bioavailability. Herin, we aimed to investigate whether berberine affects choline diet-induced arterial thrombosis and explore the potential mechanism. Ultrasound and optical coherence tomography were used to assess the potential risk of artery thrombosis in vivo. The plasma concentrations of trimethylamine N-oxide (TMAO) and trimethylamine (TMA) were quantified with mass spectrometry. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) were utilized to detect the levels of microbial TMA-lyase choline utilization C (CutC) in faeces. Gut microbiota analysis was performed with 16S rRNA gene sequencing. For in vitro studies, platelet aggregometry, intracellular Ca2+ measurement, ATP release assay, flow cytometry and Western blot were applied to identify the effects of TMAO on platelets. Berberine treatment significantly decreased the CutC levels in the caecal contents, reduced choline diet-induced TMA and TMAO production, and subsequently, reduced the arterial thrombosis potential risk. Berberine administration remodelled the structure of gut microbiota in rats and increased the levels of the genus Lactobacillus. Finally, TMAO enhanced platelet reactivity to collagen by promoting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in platelets. These results demonstrate that berberine attenuates the risk of choline diet-induced arterial thrombosis by changing the gut microbial composition and reducing TMAO generation.

Metformin inhibits cholesterol­induced adhesion molecule expression via activating the AMPK signaling pathway in vascular smooth muscle cells.

Recruitment of lymphocytes to the vascular wall contributes to the pathogenesis of atherosclerosis (AS). The expression of cellular adhesion molecules, such as vascular cell adhesion molecule­1 and intercellular adhesion molecule­1, serves a critical role in mediating lymphocyte adhesion to the vascular wall. Cholesterol loading induces the expression of adhesion molecules in vascular smooth muscle cells (VSMCs), but the underlying mechanism is not completely understood. The present study aimed to investigate the mechanism underlying the effects of cholesterol on adhesion molecule expression, and whether metformin protected VSMCs against cholesterol­induced functional alterations. Human VSMCs were loaded with cholesterol and different concentrations of metformin. The expression levels of adhesion molecules were assessed via reverse transcription­quantitative PCR and western blotting. Reactive oxygen species (ROS) accumulation and levels were quantified via fluorescence assays and spectrophotometry, respectively. AMP­activated protein kinase (AMPK), p38 MAPK and NF­κB signaling pathway­related protein expression levels were evaluated via western blotting. Compared with the control group, cholesterol loading significantly upregulated adhesion molecule expression levels on VSMCs by increasing intracellular ROS levels and activating the p38 MAPK and NF­κB signaling pathways. Metformin decreased cholesterol­induced VSMC damage by activating the AMPK signaling pathway, and suppressing p38 MAPK and NF­κB signaling. The present study indicated the therapeutic potential of metformin for VSMC protection, reduction of monocyte adhesion, and ultimately, the prevention and treatment of AS.

Computed Tomography Morphological Classification of Lung Adenocarcinoma and Its Correlation with Epidermal Growth Factor Receptor Mutation Status: A Report of 1075 Cases.

BACKGROUND: Many delayed diagnoses of lung adenocarcinoma (LADC) are identified due to poor understanding of protean imaging findings. Moreover, clarifying the relationship between computed tomography (CT) morphological classification and epidermal growth factor receptor (EGFR) mutations of LADC might inform therapeutic decision-making while obtaining pathological specimens is difficult. Here, we retrospectively analyzed CT manifestations of LADC and investigated the morphological classification of tumors in relation to EGFR mutation status. METHODS: We included 1075 LADC patients undergoing chest CT and EGFR genotype examinations from January 2013 to January 2019. CT morphological characteristics of tumors were carefully evaluated and their correlation with EGFR mutation status was analyzed using the chi-squared test. RESULTS: Tumors were divided into eight types: I (peripheral solid nodule/mass; 526/1075, 48.93%), II (central solid nodule/mass; 220/1075, 20.47%), III (subsolid nodule/mass; 92/1075, 8.56%), IV (focal consolidation; 32/1075, 2.98%), V (cystic airspace; 14/1075, 1.30%), VI (multiple lesions with similar appearances to I-V; 85/1075, 7.91%), VII (diffuse consolidation; 53/1075, 4.93%), VIII (occult lesion usually obscured by nonobstructive atelectasis; 53/1075, 4.93%). Type III and IV tumors were more frequent in patients with EGFR mutation, whereas type II and VII tumors were more common in patients without EGFR mutation (all P < 0.05). However, we did not identify any significant associations between other tumor types and EGFR mutation status (all P > 0.05). Among patients with type VI tumors, EGFR mutation status was closely related to tumor density (all P < 0.05). Furthermore, type VII tumors were associated with 19 deletion mutation positive and non-L858R mutation positive (all P < 0.05). CONCLUSION: LADC can be categorized into eight types based on CT imaging. Improving our understanding of the morphological classification and correlation with EGFR mutation status may contribute to the accurate diagnosis of LADC, while suggesting the presence of underlying EGFR genetic mutations.

Differentiating malignant and benign necrotic lung lesions using kVp-switching dual-energy spectral computed tomography.

BACKGROUND: Necrotic pulmonary lesions manifest as relatively low-density internally on contrast-enhanced computed tomography (CT). However, using CT to differentiate malignant and benign necrotic pulmonary lesions is challenging, as these lesions have similar peripheral enhancement. With the introduction of dual-energy spectral CT (DESCT), more quantitative parameters can be obtained and the ability to differentiate material compositions has been highly promoted. This study investigated the use of kVp-switching DESCT in differentiating malignant from benign necrotic lung lesions. METHODS: From October 2016 to February 2019, 40 patients with necrotic lung cancer (NLC) and 31 with necrotic pulmonary mass-like inflammatory lesion (NPMIL) were enrolled and underwent DESCT. The clinical characteristics of patients, CT morphological features, and DESCT quantitative parameters of lesions were compared between the two groups. Binary logistic regression analysis was performed to identify the independent prognostic factors differentiating NPMIL from NLC. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of single-parameter and multiparametric analyses. RESULTS: Significant differences in age, C-reactive protein concentration, the slope of the spectral curve from 40 to 65 keV (K40-65 keV) of necrosis in non-contrast-enhanced scanning (NCS), arterial phase (AP) and venous phase (VP), effective atomic number of necrosis in NCS, and iodine concentration (IC) of the solid component in VP were observed between groups (all p < 0.05). The aforementioned parameters had area under the ROC curve (AUC) values of 0.747, 0.691, 0.841, 0.641, 0.660, 0.828, and 0.754, respectively, for distinguishing between NLC and NPMIL. Multiparametric analysis showed that age, K40-65 keV of necrosis in NCS, and IC of the solid component in VP were the most effective factors for differentiating NLC from NPMIL, with an AUC of 0.966 and percentage of correct class of 88.7%. CONCLUSIONS: DESCT can differentiate malignant from benign necrotic lung lesions with a relatively high accuracy.

CT features of coronavirus disease 2019 (COVID-19) with an emphasis on the vascular enlargement pattern.

PURPOSE: The vascular enlargement (VE) pattern differs from previously described imaging patterns for pneumonia. This study aimed to investigate the incidence, computed tomography (CT) characteristics, and diagnostic value of the VE pattern in coronavirus disease 2019 (COVID-19). METHOD: The CT data of 106 patients with COVID-19 from January 19 to February 29, 2020, and 52 patients with influenza virus pneumonia (IVP) from January 2018 to February 2020 were retrospectively collected. The incidences of the VE pattern between the two groups were compared. The CT manifestations of COVID-19 were analyzed with a particular focus on the VE pattern's specific CT signs, dynamic changes, and relationships with lesion size and disease severity. RESULTS: Peripheral and multilobar ground-glass opacities (GGOs) or mixed GGOs with various sizes and morphologies were typical features of COVID-19 on initial CT. The VE pattern was more common in COVID-19 (88/106, 83.02 %) than in IVP (10/52, 19.23 %) on initial CT (P < 0.001). Three special VE-pattern-specific CT signs, including central vascular sign, ginkgo leaf sign, and comb sign, were identified. Four types of dynamic changes in the VE pattern were observed on initial and follow-up CT, which were closely associated with the evolution of lesions and the time interval from the onset of symptoms to initial CT scan. The VE pattern in COVID-19 was more commonly seen in larger lesions and patients with severe-critical type (all P < 0.001). CONCLUSIONS: The VE pattern is a valuable CT sign for differentiating COVID-19 from IVP, which correlates with more extensive or serious disease. A good understanding of the CT characteristics of the VE pattern may contribute to the early and accurate diagnosis of COVID-19 and prediction of the evolution of lesions.